Neonatal Isoerythrolysis--The Silent Stalker

Neonatal isoerythrolysis is a silent stalker of foals. At birth, the foal is normal. In some cases, the foal shows subtle signs as an internal enemy attacks and the disease progresses to a point of no return; in others, it takes only hours for the foal to go down. Neonatal isoerythrolysis (NI) debilitates the foal through the destruction of his red blood cells, leaving the foal weak, depressed, anemic, or worse. It is relatively uncommon; studies in Thoroughbreds show it occurs in less than 1% of foals. It also occurs in other breeds and in mule foals.

Most horse breeders have at least heard of the disease, even if they have not experienced the effects firsthand. The signs of NI include weakness or loss of interest in nursing, with some foals showing very little signs of a problem until it is too late.

So, what causes this disease with the difficult name, and what can you do to treat foals which have it? Are some mares at repeat risk for having NI foals? And most importantly, how can you prevent it from occurring in foals, especially if you already have experienced this disease? These questions and more will be answered in this article.

What Is NI?

Neonatal isoerythrolysis is a blood disorder that occurs in some foals less than one week of age. As stated before, the foals are not born with this disease. The problem begins when the foal nurses from the mare for the first time. As the foal ingests and absorbs the mare's colostrum, the antibodies that help protect the foal from other diseases begin to cause a disease of their own.

Mares, unlike humans, don't pass antibodies across the placenta. Therefore, if the foal does not nurse the colostrum, it will not receive protection against common "bugs" in its environment.

However, certain mares produce an antibody against a red blood cell group or factor that is transferred to the foal via the colostrum. If the foal is unfortunate enough to have that particular red blood cell group, then the antibody transferred from the mare will attack and destroy the foal's red blood cells.

In a susceptible foal, the antibodies' attack on the red blood cells results in the foal becoming anemic. The anemia can develop slowly over several days, or happen very rapidly, with the foal becoming weak, lethargic, or recumbent (unable to rise) in a matter of hours. How quickly the signs develop in the foal often is dependent on how much colostrum he absorbed and how destructive the antibodies are.

What are the signs of NI? An affected foal unfortunately does not have large scarlet letters across his chest letting everyone know what is silently occurring inside his bloodstream. This foal will, over the course of a few hours to a few days, will begin to weaken. Then it will become lethargic, have a decreased suckle response, play less, and develop pale or jaundiced mucous membranes.

Jaundice, also known as icterus, is the development of a yellow coloring of the mucous membranes (gums and whites around the eyes). As the disease progresses, these foals will develop rapid breathing (tachypnea) and rapid heart rates (tachycardia), which are caused by the decreasing number of red blood cells in their body from the disease. As the number of red blood cells decreases, the foal eventually will collapse, unable to provide enough oxygen for its brain and body to survive.

If caught early, the disease is treatable, and the foal should make a complete recovery. A foal with NI usually will develop some signs of the disease between 12 hours and four days of age. A foal which failed to drink his dam's colostrum is not at risk of NI. Your veterinarian should evaluate any foal which is acting quiet, weak, or appears sick. Other diseases, such as sepsis, can have similar signs and also require immediate attention.

Diagnosis and Treatment

The diagnosis of NI is straightforward, with anemia and jaundice being two of the most important clinical signs. After the diagnosis is established, treatment begins immediately. If the disease is recognized before the foal is 24 hours old, then the foal must be muzzled to prevent further ingestion of the mare's colostrum. The mare should be milked every two to four hours and the colostrum discarded until the foal is 24-36 hours old. During that time, the foal should be fed with an alternative milk source either by bottle, pan, or nasogastric tube. Once the mare is no longer producing colostrum, the foal can nurse from the mare freely without risk of further red blood cell damage. The foal should be monitored closely for the development of anemia and the mare and foal should be kept warm and quiet.

In most cases, the disease is not recognized until the foal is at least 24 hours old and the foal already has become anemic. Depending on the severity of the foal's anemia, a whole blood transfusion or transfusion of concentrated red blood cells might be needed. A foal is considered anemic if the packed cell volume (which measures the amount of red blood cells in the bloodstream) falls below 25-30%. Mild anemia in the foal can be treated conservatively by close monitoring and exercise restriction.

If the foal's packed cell volume falls below 12-15%, a blood transfusion usually is necessary to save the foal's life. The problem with whole blood transfusions is finding a suitable blood donor. The mare's whole blood should not be used since her plasma (liquid part of the blood) contains more of the antibodies against the foal's red blood cells, which can make a bad situation worse. However, the mare's red blood cells can be used if the plasma is discarded and the red blood cells undergo a procedure called washing, which removes any further antibodies that might be attached to the red blood cells. This procedure can take several hours to complete, so a more immediate donor often is necessary.

The sire of the foal, although usually not available, also is not a good choice for a donor, as the stallion's blood will contain the red blood cell group that the mare's antibodies are attacking. Most teaching hospitals and large private practices have a blood donor available which has been typed, usually an older gelding. A cross match is necessary prior to administering the blood to the foal to prevent a transfusion reaction. Once the transfusion is administered, the foal is monitored for any complications or further anemia, but this treatment should be curative.

A new treatment--a synthetic blood product--recently became available. This product can carry oxygen throughout the body (which is the function of red blood cells) without the risk of transfusion reactions from regular blood. A blood substitute can be given to the severely anemic foal immediately while a cross match procedure is being done at the laboratory (which can take up to two hours on normal equine blood). The blood substitute saves valuable time and sometimes means the difference between life and death for the foal. However, the synthetic blood is only a temporary treatment, and normal equine blood must be administered.

Risk Factors

What mares are at risk of having NI foals? Neonatal isoerythrolysis develops when the mare becomes sensitized (develops antibodies) to certain red blood cell factors. Horses--like people--have different blood types. However, horses have eight "major" blood types, with many different alloantigens possible. For example, type A blood has Aa, Ab, and Ac alloantigens. If the mare lacks a particular red blood cell factor such as Aa and is exposed to the "foreign" factor, then she will form antibodies against that factor. Mares can develop these red blood cell factor antibodies two ways: The mare can be exposed to the foreign red blood cell factor during a blood transfusion, or by being exposed to a foreign blood group or factor present in a foal's blood during the birthing process. After exposure to the foreign blood factor, she will make antibodies against it, which will circulate in her bloodstream throughout her life.

Although the mare might have antibodies against certain red blood cell factors circulating in her bloodstream, if the mare and foal have incompatible blood types, the foal will not be affected while in utero since the equine placenta does not allow crossover of antibodies from the mare to the fetus. Furthermore, the foal will not be affected unless it has inherited the foreign red blood cell factor from the sire. If the foal has the red cell factor to which the mare has antibodies, then the foal will develop NI when it ingests the mare's colostrum that contains the antibodies against the particular red blood cell factor.

The two main culprits in NI are the A and Q blood groups, and more specifically the Aa and Qa alloantigens. However, in theory, any blood group the mare lacks and the stallion and foal possess could present a problem. In reality, the A and Q groups appear to be the ones that cause the vast majority of the problems with NI foals.

Mares which lack these two groups are at the highest risk for producing NI-causing antibodies. Mares can be screened for these factors by blood-typing, and if the mare is negative for the factors A or Q, then preventative measures might need to be taken.

Mares bred to donkeys to produce mule foals also can be at risk for producing NI mule foals. These mares are almost all at risk for developing antibodies to a red blood cell factor called the "donkey factor." The mares are at risk because they do not innately possess the factor. However, they must be exposed to this factor to develop antibodies against it. If exposed, usually through mixing of the mare's blood with the mule foal's blood at birth, then they can produce antibodies capable of producing NI.

Maiden mares are not at risk for developing antibodies against the foal's red blood cell factor unless they have had a blood transfusion at some point before foaling. Mares which develop the antibodies are ones which have had several foals and have been exposed at some point to the blood of one of their foals. Furthermore, developing these antibodies and having a foal develop NI is not a one-time event; once a mare has had a NI foal, the possibility of a subsequent foal developing the disease is possible. Therefore, prevention is the key.

Preventing NI

Once a mare has produced a NI foal or has had a blood transfusion, then several procedures can be done to predict--then prevent--the occurrence of this disease. If the mare is lacking the A or Q blood groups and has developed antibodies to one or both of those factors, then breeding the mare to a stallion which also lacks those factors is one way of preventing the disease. This results in a foal which doesn't possess the foreign antigen. Without the offending red cell group, the foal's other red blood cells will be unaffected by the antibodies in the colostrum. However, the A and Q factors are very common, and it is sometimes difficult to find a stallion with all of the other desirable physical and competitive attributes you want, in addition to the appropriate blood type. This is often not practical or even feasible, so other measures must be taken.

If a NI foal is likely, one basic method of prevention is ensuring that the birth is attended and the foal is prevented from drinking the mare's colostrum. The foal should be muzzled and the dam's colostrum milked and discarded for the first 24 hours. The foal will require another source of antibodies, so it either must be fed other (tested) colostrum or be administered intravenous or oral immunoglobulins. The foal also will require some type of milk replacer for the first 24 hours of life. After 24 hours, the foal can nurse from the dam normally.

There are several different tests that can be performed while the mare is pregnant and at the time of birth to determine if NI is likely with a particular foal, therefore determining whether withholding the mare's colostrum is necessary.

Mares can be tested late in pregnancy (within 30 days of foaling) to determine if they have red blood cell antibodies present. If the laboratory finds that the mare has a certain level of antibodies, then it would be recommended to withhold the mare's colostrum from the foal; then preparations can be made early to find an alternative source of colostrum and milk.

Testing also can be performed immediately after foaling. Blood from the mare and foal is collected, and a blood cross-match is performed to determine if the mare has red blood cell antibodies that will react against the newborn foal's blood and cause jaundice. If the test is positive, then an alternative source of colostrum must be found immediately. This test usually is performed in a laboratory, and it might not be available in the middle of the night.

An "in the field" cross-match test can be performed by your veterinarian just after foaling. This test can determine whether the mare's colostrum contains antibodies against the foal's red blood cells. This test is called a "jaundice foal agglutination test" and requires only basic lab equipment, so most veterinarians can perform it on the farm or in a clinic setting. If this test is positive, then the mare's colostrum cannot be used and an alternative source of colostrum and milk is needed.

(Each newborn foal--with or without the risk of NI--should have its IgG level checked before 24 hours of age to determine whether or not the foal has absorbed enough immunoglobulins to protect it against infection. The best treatment for failure of passive transfer is prevention by testing and having a source of suitable colostrum available.)

If you have a mare with risk factors for producing NI foals, consult your veterinarian for the best advice, then formulate a plan to help eliminate the risk of dealing with a jaundiced foal.